Discordant bioinformatic predictions of antimicrobial resistance from whole-genome sequencing data of bacterial isolates: an inter-laboratory study.

Antimicrobial resistance (AMR) poses a threat to public health. Clinical microbiology laboratories typically rely on culturing bacteria for antimicrobial-susceptibility testing (AST). As the implementation costs and technical barriers fall, whole-genome sequencing (WGS) has emerged as a 'one-stop' test for epidemiological and predictive AST results. Few published comparisons exist for the myriad analytical pipelines used for predicting AMR. To address this, we performed an inter-laboratory study providing sets of participating researchers with identical short-read WGS data from clinical isolates, allowing us to assess the reproducibility of the bioinformatic prediction of AMR between participants, and identify problem cases and factors that lead to discordant results. We produced ten WGS datasets of varying quality from cultured carbapenem-resistant organisms obtained from clinical samples sequenced on either an Illumina NextSeq or HiSeq instrument. Nine participating teams ('participants') were provided these sequence data without any other contextual information. Each participant used their choice of pipeline to determine the species, the presence of resistance-associated genes, and to predict susceptibility or resistance to amikacin, gentamicin, ciprofloxacin and cefotaxime. We found participants predicted different numbers of AMR-associated genes and different gene variants from the same clinical samples. The quality of the sequence data, choice of bioinformatic pipeline and interpretation of the results all contributed to discordance between participants. Although much of the inaccurate gene variant annotation did not affect genotypic resistance predictions, we observed low specificity when compared to phenotypic AST results, but this improved in samples with higher read depths. Had the results been used to predict AST and guide treatment, a different antibiotic would have been recommended for each isolate by at least one participant. These challenges, at the final analytical stage of using WGS to predict AMR, suggest the need for refinements when using this technology in clinical settings. Comprehensive public resistance sequence databases, full recommendations on sequence data quality and standardization in the comparisons between genotype and resistance phenotypes will all play a fundamental role in the successful implementation of AST prediction using WGS in clinical microbiology laboratories

Association of treatment satisfaction and psychopathological sub-syndromes among involuntary patients with psychotic disorders

Publisher's version: http://www.springerlink.com/content/rx24036274667t10

Allelic based gene-gene interactions in rheumatoid arthritis

The detection of gene-gene interaction is an important approach to understand the etiology of rheumatoid arthritis (RA). The goal of this study is to identify gene-gene interaction of SNPs at the allelic level contributing to RA using real data sets (Problem 1) of North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Analysis Workshop 16 (GAW16). We applied our novel method that can detect the interaction by a definition of nonrandom association of alleles that occurs when the contribution to RA of a particular allele inherited in one gene depends on a particular allele inherited at other unlinked genes. Starting with 639 single-nucleotide polymorphisms (SNPs) from 26 candidate genes, we identified ten two-way interacting genes and one case of three-way interacting genes. SNP rs2476601 on PTPN22 interacts with rs2306772 on SLC22A4, which interacts with rs881372 on TRAF1 and rs2900180 on C5, respectively. SNP rs2900180 on C5 interacts with rs2242720 on RUNX1, which interacts with rs881375 on TRAF1. Furthermore, rs2476601 on PTPN22 also interacts with three SNPs (rs2905325, rs1476482, and rs2106549) in linkage disequilibrium (LD) on IL6. The other three SNPs (rs2961280, rs2961283, and rs2905308) in LD on IL6 interact with two SNPs (rs477515 and rs2516049) on HLA-DRB1. SNPs rs660895 and rs532098 on HLA-DRB1 interact with rs2834779 and four SNPs in LD on RUNX1. Three-way interacting genes of rs10229203 on IL6, rs4816502 on RUNX1, and rs10818500 on C5 were also detected

Prevention and management of excessive gestational weight gain: a survey of overweight and obese pregnant women

Background - Excessive gestational weight gain is associated with adverse infant, childhood and maternal outcomes and research to develop interventions to address this issue is ongoing. The views of women on gestational weight gain and the resources they would consider helpful in addressing this are however largely unknown. This survey aimed to determine the views of newly pregnant women, living in areas of social disadvantage, on 1) their current body weight and potential gestational weight gain and 2) the resources or interventions they would consider helpful in preventing excessive gestational weight gain. Methods - A convenience sample of overweight and obese pregnant women living in Fife, UK, were invited to complete a short anonymised questionnaire at their 12 week booking visit. Results - 428 women, BMI>25 kg/m2, completed the questionnaire. Fifty-four per cent of respondents were obese (231) and 62% were living in areas of mild to moderate deprivation. Over three-quarters of participants felt dissatisfied with their current weight (81%). The majority of women (60%) expressed some concern about potential weight gain. Thirty-nine percent were unconcerned about weight gain during their pregnancy, including 34 women (19%) who reported having retained weight gained in earlier pregnancies. Amongst those concerned about weight gain advice on physical activity (41%) and access to sports/leisure facilities were favoured resources (36%). Fewer women (12%) felt that group sessions on healthy eating or attending a clinic for individualised advice (14%) would be helpful. "Getting time off work" was the most frequently cited barrier (48%) to uptake of resources other than leaflets. Conclusions- These data suggest a lack of awareness amongst overweight and obese women regarding excessive gestational weight gain. Monitoring of gestational weight gain, and approaches for its management, should be formally integrated into routine antenatal care. Barriers to the uptake of resources to address weight gain are numerous and must be considered in the design of future interventions and services

The stigma of obesity in the general public and its implications for public health - a systematic review

<p>Abstract</p> <p>Background</p> <p>Up to this date, prevalence rates of obesity are still rising. Aside from co-morbid diseases, perceived discrimination and stigmatization leads to worsen outcomes in obese individuals. Higher stigmatizing attitudes towards obese individuals may also result in less support of preventive and interventive measures. In light of the immense burden of obesity on health care systems and also on the individuals' quality of life, accepted and subsidized preventive measures are needed. Policy support might be determined by views of the lay public on causes of obesity and resulting weight stigma. This study seeks to answer how representative samples of the lay public perceive people with obesity or overweight status (stigmatizing attitudes); what these samples attribute obesity to (causal attribution) and what types of interventions are supported by the lay public and which factors determine that support (prevention support).</p> <p>Methods</p> <p>A systematic literature search was conducted. All studies of representative samples reporting results on (a) stigmatizing attitudes towards overweight and obese individuals, (b) causal beliefs and (c) prevention support were included.</p> <p>Results</p> <p>Only 7 articles were found. One study reported prevalence rates of stigmatizing attitudes. About a quarter of the population in Germany displayed definite stigmatizing attitudes. Other studies reported causal attributions. While external influences on weight are considered as well, it seems that internal factors are rated to be of higher importance. Across the studies found, regulative prevention is supported by about half of the population, while childhood prevention has highest approval rates. Results on sociodemographic determinants differ substantially.</p> <p>Conclusions</p> <p>Further research on public attitudes toward and perception of overweight and obesity is urgently needed to depict the prevailing degree of stigmatization. Introducing a multidimensional concept of the etiology of obesity to the lay public might be a starting point in stigma reduction.</p

How and why weight stigma drives the obesity 'epidemic' and harms health.

BACKGROUND:In an era when obesity prevalence is high throughout much of the world, there is a correspondingly pervasive and strong culture of weight stigma. For example, representative studies show that some forms of weight discrimination are more prevalent even than discrimination based on race or ethnicity. DISCUSSION:In this Opinion article, we review compelling evidence that weight stigma is harmful to health, over and above objective body mass index. Weight stigma is prospectively related to heightened mortality and other chronic diseases and conditions. Most ironically, it actually begets heightened risk of obesity through multiple obesogenic pathways. Weight stigma is particularly prevalent and detrimental in healthcare settings, with documented high levels of 'anti-fat' bias in healthcare providers, patients with obesity receiving poorer care and having worse outcomes, and medical students with obesity reporting high levels of alcohol and substance use to cope with internalized weight stigma. In terms of solutions, the most effective and ethical approaches should be aimed at changing the behaviors and attitudes of those who stigmatize, rather than towards the targets of weight stigma. Medical training must address weight bias, training healthcare professionals about how it is perpetuated and on its potentially harmful effects on their patients. CONCLUSION:Weight stigma is likely to drive weight gain and poor health and thus should be eradicated. This effort can begin by training compassionate and knowledgeable healthcare providers who will deliver better care and ultimately lessen the negative effects of weight stigma

Liver injury and fibrosis induced by dietary challenge in the ossabaw miniature Swine

BACKGROUND: Ossabaw miniature swine when fed a diet high in fructose, saturated fat and cholesterol (NASH diet) develop metabolic syndrome and nonalcoholic steatohepatitis (NASH) characterized by liver injury and fibrosis. This study was conducted to further characterize the development of NASH in this large animal model. METHODS: Ossabaw swine were fed standard chow (control group; n = 6) or NASH diet (n = 6) for 24 weeks. Blood and liver tissue were collected and liver histology were characterized at 0, 8, 16 and 24 weeks of dietary intervention. Hepatic apoptosis and lipid levels were assessed at week 24. RESULTS: The NASH diet group developed metabolic syndrome and progressive histologic features of NASH including: (a) hepatocyte ballooning at 8 weeks which progressed to extensive ballooning (>90% hepatocytes), (b) hepatic fibrosis at week 16, which progressed to moderate fibrosis, and (c) Kupffer cell accumulation with vacuolization at 8 weeks which progressed through week 24. The NASH diet group showed increased hepatocyte apoptosis that correlated with hepatic total and free cholesterol and free fatty acids, but not esterified cholesterol or triglycerides. CONCLUSIONS: This report further characterizes the progression of diet-induced NASH in the Ossabaw swine model. In Ossabaw swine fed the NASH diet: (a) hepatocyte injury and fibrosis can occur without macrovesicular steatosis or excess triglyceride accumulation; (b) hepatocyte ballooning generally precedes the development of fibrosis; (c) there is increased hepatocyte apoptosis, and it is correlated more significantly with hepatic free cholesterol than hepatic free fatty acids and had no correlation with hepatic triglycerides

The context of chemical communication driving a mutualism

Recent work suggests that Drosophila and Saccharomyces yeasts may establish a mutualistic association, and that this is driven by chemical communication. While individual volatiles have been implicated in the attraction of D. melanogaster, the semiochemicals affecting the behavior of the sibling species D. simulans are less well characterised. Here, we comprehensively scrutinize a broad range of volatiles produced by attractive and repulsive yeasts to experimentally evaluate the chemical nature of communication between these species. When grown in liquid or on agar-solidified grape juice, attraction to S. cerevisiae was primarily driven by 3-methylbutyl acetate (isoamyl acetate) and repulsion by acetic acid, a known attractant to D. melanogaster (also known as vinegar fly). Using T-maze choice tests and synthetic compounds we show that these responses were strongly influenced by compound concentration. Moreover, the behavioral response is further impacted by the chemical context of the environment. Thus, chemical communication between yeasts and flies is complex, and is not simply driven by the presence of single volatiles, but modulated by compound interactions. The ecological context of chemical communication needs to be taken into consideration when testing for ecologically realistic responses

Misuse of "study drugs:" prevalence, consequences, and implications for policy

BACKGROUND: Non-medical/illegal use of prescription stimulants popularly have been referred to as "study drugs". This paper discusses the current prevalence and consequences of misuse of these drugs and implications of this information for drug policy. RESULTS: Study drugs are being misused annually by approximately 4% of older teens and emerging adults. Yet, there are numerous consequences of misuse of prescription stimulants including addiction, negative reactions to high dosages, and medical complications. Policy implications include continuing to limit access to study drugs, finding more safe prescription drug alternatives, interdiction, and public education. CONCLUSION: Much more work is needed on prescription stimulant misuse assessment, identifying the extent of the social and economic costs of misuse, monitoring and reducing access, and developing prevention and cessation education efforts